Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava–Bignami disease

Abstract

Ethanol is an important risk factor for the occurrence of several brain disorders that depend on the amount, period and frequency of its consumption. Chronic use of ethanol often leads to the development of neurodegenerative syndromes, which cause morphological and functional impairments such as foetal alcohol syndrome in newborns exposed to ethanol during pregnancy, Wernicke-Korsakoff Syndrome and, more rarely, Marchiafava-Bignami disease (MBD). MBD is characterized by primary degeneration of the corpus callosum, without inflammation and is associated with oxidative stress and hypovitaminosis, as well as altered mental status, to mention dementia, seizures, depression and so on. This review discusses MBD and poor nutrition as a risk factor for the development of such alcoholic syndrome, with focus on diagnosis, pathogenic aspects, signs and symptoms, as well as therapeutic perspectives. On the basis of the inclusion/exclusion criteria adopted, the performed search in scientific databases (Pubmed, Scielo and Google Scholar) resulted in 100 studies that are being presented and discussed in the present work. Review, case-control and cohort studies on alcoholism-associated hypovitaminosis, oxidative stress, MBD and ethanol metabolism pathways were admitted as relevant. We highlight that MBD is a poorly described, diagnosed, insidious and progressive condition, for which evidence suggests a synergism between ethanol-induced neurotoxic effects and hypovitaminosis B. Present treatment consists of vitamin B1(thiamine) supplementation. Nonetheless, other strategies such as the inclusion of antidepressants or steroidal anti-inflammatories as add-on therapies have been employed as an attempt to improve the damage. Indeed, both the diagnosis and treatment are difficult, and death occurs within few years.

Thiamine deficiency activates hypoxia inducible factor-1α to facilitate pro-apoptotic responses in mouse primary astrocytes

“…Alternatively, an increase in ROS generated by complex III of the electron transport chain (ETC) has been implicated in HIF-1α stabilization following H/I [ 75 ]. An abundance of ROS is a consequence of mitochondrial dysfunction in TD brains [ 11 , 80 ]. A reduction in α-KGDH activity induces mitochondrial uncoupling and oxidative stress in astrocytes [ 38 ].…”

Rapidly Resolving Nonalcoholic Marchiafava-Bignami Disease in the Setting of Malnourishment After Gastric Bypass Surgery

“…The dosing regimen for thiamine and folate were chosen partly from the doses used in alcoholics to prevent Wernicke-Korsakoff syndrome. 4 , 5 Other B vitamins including pyridoxine and cyanocobalamin have been studied as well, though there is no standard dose. We made the clinical decision to use all 4 given the patient’s known malnutrition and very low negative effects of vitamin administration.…”

Wernicke Encephalopathy—Clinical Pearls

“…It can present in a similar fashion as WE and should be considered in the differential diagnosis. 15 However, performing MRI on an emergent basis for this indication is cumbersome. Overall, thiamine administration, either in high or low dosage, is considered low risk and untreated patients could have serious adverse consequences.…”